Extended functional repertoire for human copper chaperones

2016 ◽  
Vol 7 (1) ◽  
pp. 29-39 ◽  
Author(s):  
Maria Matson Dzebo ◽  
Candan Ariöz ◽  
Pernilla Wittung-Stafshede
Keyword(s):  
Transport Systems ◽  
Control Mechanisms ◽  
Superoxide Dismutase 1 ◽  
Copper Chaperones ◽  
Chaperone Function ◽  
Regulatory Processes ◽  
Interaction Partners ◽  
Future Drug ◽  
Golgi Network ◽  
Cu Ions

AbstractCopper (Cu) ions are cofactors in many essential enzymes. As free Cu ions are toxic, most organisms have highly specialized Cu transport systems involving dedicated proteins. The human cytoplasmic Cu chaperone Atox1 delivers Cu to P1B-type ATPases in the Golgi network, for incorporation into Cu-dependent enzymes following the secretory path. Atox1 homologs are found in most organisms; it is a 68-residue ferredoxin-fold protein that binds Cu in a conserved surface-exposed CXXC motif. In addition to Atox1, the human cytoplasm also contains Cu chaperones for loading of superoxide dismutase 1 (i.e. CCS) and cytochrome c oxidase in mitochondria (i.e. Cox17). Many mechanistic aspects have been resolved with respect to how Cu ions are moved between these proteins. In addition to the primary cytoplasmic Cu chaperone function, all three cytoplasmic chaperones have been reported to have other interaction partners that are involved in signaling pathways that modulate cell growth and development. These new discoveries imply that humans have evolved a highly sophisticated network of control mechanisms that connect Cu transport with cell regulatory processes. This knowledge may eventually be exploited for future drug developments towards diseases such as cancer and neurodegenerative disorders.

scholarly journals Perceptions on Regulation and Asymmetry of Information as Critical Factors in University Governance in Latin America

SAGE Open ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 215824402110231
Author(s):  
Juan Bautista Abello-Romero ◽  
Daniel López ◽  
Francisco Ganga ◽  
Claudio Mancilla
Keyword(s):  
Latin American ◽  
Influential Factors ◽  
Control Mechanisms ◽  
American University ◽  
American Universities ◽  
Asymmetry Of Information ◽  
Regulatory Processes ◽  
National Differences ◽  
The Board Of Directors ◽  
Latin American Universities

This article analyzes the results of an inquiry into Latin American university community members’ perceptions about regulatory processes and asymmetries of information, as influential factors in the governance of Latin American universities. It does so, by examining the national laws in Argentina, Brazil, Colombia, Chile, and Mexico. Previous studies in this continent have not considered these aspects and perspectives. Our research found significant differences between countries in terms of the Board of Directors’ capacity to act and the control mechanisms they can employ—which can be interpreted as national differences in the availability of their resources and their regulatory capacities. On the level of asymmetry of information, there are differences between countries, which depend on the position of the university members in their institutions. Thus, regulation and information are important factors when it comes to the governance of Latin American universities, and can explain its’ diversity.

Neurocognitive underpinnings of social development during childhood

2021 ◽  
Author(s):  
Nikolaus Steinbeis
Keyword(s):  
Social Control ◽  
Social Development ◽  
Middle Childhood ◽  
Behavioral Control ◽  
Control Mechanisms ◽  
Social Phenomena ◽  
Prefrontal Cortical ◽  
Regulatory Processes ◽  
Subcortical Regions ◽  
Cortical Regions

This chapter reviews the neurocognitive mechanisms underlying social development during middle childhood. The author focuses on social abilities (e.g., theory of mind and empathy) and prosocial behavior (e.g., sharing and helping). The chapter discusses studies and theories on developmental changes in these social phenomena and references evidence of neurocognitive underpinnings where available. The author argues that changes in social development during childhood can best be explained in developments in regulatory processes, such as behavioral control, emotion regulation, conflict processing, and self-other control. The author refers to this cluster of functions as social control mechanisms. Changes in these social control mechanisms are driven by the maturation of neural circuitry comprising prefrontal cortical regions and their interactions with subcortical regions. Crucially, while the neurocognitive mechanisms underlying social development are distinct for different abilities and behaviors, it appears to be domain-general processes that predominantly shape social development during middle childhood.

scholarly journals Renal and small intestinal sodium-dependent symporters of phosphate and sulphate.

1994 ◽  
Vol 196 (1) ◽  
pp. 167-181
Author(s):  
H Murer ◽  
D Markovich ◽  
J Biber
Keyword(s):  
Apical Membrane ◽  
Transport Systems ◽  
Expression Cloning ◽  
Control Mechanisms ◽  
Intestinal Epithelial ◽  
Physiological Conditions ◽  
Sodium Dependent ◽  
Proximal Tubular ◽  
Small Intestinal ◽  
Dependent Transport

Homeostasis of inorganic phosphate (P(i)) and sulphate (Si) is largely achieved by absorption in the mammalian small intestine and by reabsorption in the proximal tubule of the kidney. Under normal physiological conditions, the kidney appears to play the major role in maintaining the extracellular concentration of these anions. In both epithelia, reabsorption of P(i) and to some extent also of Si underlie a variety of regulatory acute and chronic control mechanisms. Acute regulatory mechanisms are predominantly found in renal P(i) reabsorption, whereas chronic regulation of transepithelial P(i) transport is observed in both tissues. Also, in both epithelia, apically located sodium-dependent transport systems (Na+/P(i) and Na+/Si symport) represent major targets for known regulatory factors. By expression cloning using oocytes of Xenopus laevis, renal and small intestinal Na(+)-dependent phosphate and sulphate transport systems have been identified. Evidence has been obtained that cloned Na+/P(i) and Na+/Si symporters are localized in the apical membrane of proximal tubular or small intestinal epithelial cells respectively. Furthermore, recent results indicate that one of the cloned Na+/P(i) symporters is involved in the physiological and pathophysiological regulation of proximal tubular P(i) reabsorption.

scholarly journals Division of labor in metabolic regulation by transcription, translation, acetylation and phosphorylation

2019 ◽  
Author(s):  
Sriram Chandrasekaran
Keyword(s):  
Metabolic Regulation ◽  
Metabolic Networks ◽  
Network Connectivity ◽  
Control Mechanisms ◽  
Post Translational Modifications ◽  
Regulatory Processes ◽  
Regulatory Architecture ◽  
A Cell ◽  
Metabolic Properties ◽  
Context Specific

AbstractThe metabolism of most organisms is controlled by a diverse cast of regulatory processes, including transcriptional regulation and post-translational modifications (PTMs). Yet how metabolic control is distributed between these regulatory processes is unknown. Here we present Comparative Analysis of Regulators of Metabolism (CAROM), an approach that compares regulators based on network connectivity, flux, and essentiality of their reaction targets. Using CAROM, we analyze transcriptome, proteome, acetylome and phospho-proteome dynamics during transition to stationary phase in E. coli and S. cerevisiae. CAROM uncovered that the targets of each regulatory process shared unique metabolic properties: growth-limiting reactions were regulated by acetylation, while isozymes and futile-cycles were preferentially regulated by phosphorylation. Reversibility, essentiality, and molecular-weight further distinguished reactions controlled through diverse mechanisms. While every enzyme can be potentially regulated by multiple mechanisms, analysis of context-specific datasets reveals a conserved partitioning of metabolic regulation based on reaction attributes.Author summaryThere are several ways to regulate an enzyme’s activity in a cell. Yet, the design principles that determine when an enzyme is regulated by transcription, translation or post-translational modifications are unknown. Each control mechanism, such as transcription, comprises several regulators that control a distinct set of targets. So far, it is unclear if similar partitioning of targets occurs at a higher level, between different control mechanisms. Here we systematically analyze patterns of metabolic regulation in model microbes. We find that five key parameters can distinguish the targets of each mechanism. These key parameters provide insights on specific roles played by each mechanism in determining overall metabolic activity. This approach may help define the basic regulatory architecture of metabolic networks.

scholarly journals Rheb and mammalian target of rapamycin in mitochondrial homoeostasis

Open Biology ◽  
2013 ◽  
Vol 3 (12) ◽  
pp. 130185 ◽  
Author(s):  
Marlous J. Groenewoud ◽  
Fried J. T. Zwartkruis
Keyword(s):  
Transcription Factors ◽  
Mammalian Target Of Rapamycin ◽  
Glycolytic Flux ◽  
Control Mechanisms ◽  
Metabolic Intermediates ◽  
Unfolded Protein ◽  
Regulatory Processes ◽  
Growth Promoting ◽  
The Unfolded Protein Response ◽  
Protein Response

Mitochondrial dysfunction has been associated with various diseases, such as cancer, myopathies, neurodegeneration and obesity. Mitochondrial homoeostasis is achieved by mechanisms that adapt the number of mitochondria to that required for energy production and for the supply of metabolic intermediates necessary to sustain cell growth. Simultaneously, mitochondrial quality control mechanisms are in place to remove malfunctioning mitochondria. In the cytoplasm, the protein complex mTORC1 couples growth-promoting signals with anabolic processes, in which mitochondria play an essential role. Here, we review the involvement of mTORC1 and Rheb in mitochondrial homoeostasis. The regulatory processes downstream of mTORC1 affect the glycolytic flux and the rate of mitophagy, and include regulation of the transcription factors HIF1α and YY1/PGC-1α. We also discuss how mitochondrial function feeds back on mTORC1 via reactive oxygen species signalling to adapt metabolic processes, and highlight how mTORC1 signalling is integrated with the unfolded protein response in mitochondria, which in Caenorhabditis elegans is mediated via transcription factors such as DVE-1/UBL-5 and ATFS-1.

scholarly journals The Calcium/Calmodulin-Dependent Kinases II and IV as Therapeutic Targets in Neurodegenerative and Neuropsychiatric Disorders

2021 ◽  
Vol 22 (9) ◽  
pp. 4307
Author(s):  
Kinga Sałaciak ◽  
Aleksandra Koszałka ◽  
Elżbieta Żmudzka ◽  
Karolina Pytka
Keyword(s):  
Drug Design ◽  
Therapeutic Targets ◽  
Neuropsychiatric Disorders ◽  
Cellular Functions ◽  
Calcium Calmodulin Dependent ◽  
Regulatory Processes ◽  
Neuropsychiatric Diseases ◽  
Future Drug ◽  
Structure And Functions

CaMKII and CaMKIV are calcium/calmodulin-dependent kinases playing a rudimentary role in many regulatory processes in the organism. These kinases attract increasing interest due to their involvement primarily in memory and plasticity and various cellular functions. Although CaMKII and CaMKIV are mostly recognized as the important cogs in a memory machine, little is known about their effect on mood and role in neuropsychiatric diseases etiology. Here, we aimed to review the structure and functions of CaMKII and CaMKIV, as well as how these kinases modulate the animals’ behavior to promote antidepressant-like, anxiolytic-like, and procognitive effects. The review will help in the understanding of the roles of the above kinases in the selected neurodegenerative and neuropsychiatric disorders, and this knowledge can be used in future drug design.

Bi-directional trafficking between the trans-Golgi network and the endosomal/lysosomal system

2000 ◽  
Vol 113 (12) ◽  
pp. 2093-2101 ◽  
Author(s):  
W.M. Rohn ◽  
Y. Rouille ◽  
S. Waguri ◽  
B. Hoflack
Keyword(s):  
Molecular Mechanisms ◽  
Protein Transport ◽  
Transport Systems ◽  
Membrane Glycoproteins ◽  
Trans Golgi Network ◽  
Sorting Signals ◽  
Lysosomal System ◽  
Golgi Network ◽  
Endosomal System ◽  
Assembly Proteins

Protein transport in the secretory and endocytic pathways of eukaryotic cells is mediated by vesicular transport intermediates. Their formation is a tightly controlled multistep process in which coat components are recruited onto specific membranes, and cargo, as well as targeting molecules, become segregated into nascent vesicles. At the trans-Golgi network, two transport systems deliver cargo molecules to the endosomal system. They can be distinguished with regard to coat components that select cargo molecules. AP-1 assembly proteins mediate transport of MPRs and furin, whereas AP-3 adaptors mediate transport of lysosomal membrane glycoproteins to the endosomal/lysosomal system. The molecular basis for protein-specific sorting lies within sorting signals that are present in the cytoplasmic tails of cargo proteins and allow specific interactions with individual coat components. In order to maintain cellular homeostasis, some proteins are retrieved from endosomal compartments and transported back to the trans-Golgi network. Distinct points for protein retrieval exist within the endosomal system, retrieval occurring from either early or late endosomes. Whereas significant progress has been made in recent years in identifying anterograde and retrograde transport pathways, the molecular mechanisms underlying protein sorting and retrieval are only poorly defined. Recently, however, novel vesicle coats (e.g. AP-4) and proteins that might be involved in sorting (e.g. PACS-1 and TIP47) have been described, and the interactions between assembly proteins and sorting signals are becoming increasingly well defined.

scholarly journals Copper transporters and copper chaperones: roles in cardiovascular physiology and disease

2018 ◽  
Vol 315 (2) ◽  
pp. C186-C201 ◽  
Author(s):  
Tohru Fukai ◽  
Masuko Ushio-Fukai ◽  
Jack H. Kaplan
Keyword(s):  
Wound Repair ◽  
Lysyl Oxidase ◽  
Transport Systems ◽  
Copper Chaperones ◽  
Physiological Processes ◽  
Cardiovascular Biology ◽  
Matrix Stability ◽  
Cardiovascular Cells ◽  
And Function ◽  
Frequent Presence

Copper (Cu) is an essential micronutrient but excess Cu is potentially toxic. Its important propensity to cycle between two oxidation states accounts for its frequent presence as a cofactor in many physiological processes through Cu-containing enzymes, including mitochondrial energy production (via cytochrome c-oxidase), protection against oxidative stress (via superoxide dismutase), and extracellular matrix stability (via lysyl oxidase). Since free Cu is potentially toxic, the bioavailability of intracellular Cu is tightly controlled by Cu transporters and Cu chaperones. Recent evidence reveals that these Cu transport systems play an essential role in the physiological responses of cardiovascular cells, including cell growth, migration, angiogenesis and wound repair. In response to growth factors, cytokines, and hypoxia, their expression, subcellular localization, and function are tightly regulated. Cu transport systems and their regulators have also been linked to various cardiovascular pathophysiologies such as hypertension, inflammation, atherosclerosis, diabetes, cardiac hypertrophy, and cardiomyopathy. A greater appreciation of the central importance of Cu transporters and Cu chaperones in cell signaling and gene expression in cardiovascular biology offers the possibility of identifying new therapeutic targets for cardiovascular disease.

The Dynamics and Control of Chemical Processes in Man

1970 ◽  
Vol 3 (10) ◽  
pp. T157-T167 ◽  
Author(s):  
E. R. Carson ◽  
L. Finkelstein
Keyword(s):  
Protein Metabolism ◽  
Compartmental Analysis ◽  
Chemical Processes ◽  
Transport Systems ◽  
Control Mechanisms ◽  
Bilirubin Metabolism ◽  
Dynamics And Control ◽  
Modelling Techniques ◽  
Systems Modelling ◽  
And Control

The paper reviews the various control mechanisms to be found in chemical reactions occurring in man. The concept of compartmental analysis is discussed and the unit processes of biochemistry are considered, e.g. enzymic reactions, expanding systems, transport systems. Modelling techniques are discussed with particular reference to plasma protein metabolism and bilirubin metabolism.

Predicate Based Caching for Large Scale Mobile Distributed On-line Applications

2003 ◽  
pp. 112-135
Author(s):  
Abhinav Vora ◽  
Zahir Tari ◽  
Peter Bertok
Keyword(s):  
Large Scale ◽  
Transport Systems ◽  
Mobile Object ◽  
Binary Representation ◽  
Control Mechanisms ◽  
Data Interoperability ◽  
Available Bandwidth ◽  
Mobility Data ◽  
Cache Invalidation ◽  
Cache Manager

Robust mobile middlewares are crucial for online applications as they provide solutions for the core issues of mobility, data interoperability, and security. This chapter describes our experience in designing such middlewares for one of the largest Australian transport companies (CMS Transport Systems). We focus on the design of a predicate-based caching technique for mobile object-based middlewares that optimises the performance of the mobile medium by better utilising the available bandwidth. Several caching techniques have been proposed to improve system and application performance. Such techniques, along with consistency control mechanisms, are used to reduce the communication load between clients and servers, which is particularly important in wireless networks. Caching techniques are generally classified as either ID-based or predicate-based. In this chapter we propose a predicate-based caching scheme, in which the predicates are used in combination with updates and are broadcast by servers in a set of appropriate messages called cache invalidation reports. Each report/message contains information about the data items that have been updated in the server during a given period. A function mapping the predicate into binary representation is defined for each attribute. Because not all updates are relevant to a cache, there is a matching algorithm for detecting relevancy between the cache predicate and the predicates in the cache invalidation reports. The predicate-based cache invalidation reports inform the client cache manager concisely about items that need to be refreshed and about those that need to be discarded, and ensure efficient bandwidth usage.

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